ICTV VIRUS TAXONOMY PROFILES Cotmore et al., Journal of General Virology 2019;100:367–368 DOI 10.1099/jgv.0.001212 ICTV ICTV Virus Taxonomy Profile: Parvoviridae Susan F. Cotmore,1,* Mavis Agbandje-McKenna,2 Marta Canuti,3 John A. Chiorini,4 Anna-Maria Eis-Hubinger,5 Joseph Hughes,6 Mario Mietzsch,2 Sejal Modha,6 Mylene Ogliastro,7 Judit J. Penzes, 2 David J. Pintel,8 Jianming Qiu,9 Maria Soderlund-Venermo,10 Peter Tattersall,1,11 Peter Tijssen12 and ICTV Report Consortium Abstract Members of the family Parvoviridae are small, resilient, non-enveloped viruses with linear, single-stranded DNA genomes of 4–6 kb. Viruses in two subfamilies, the Parvovirinae and Densovirinae, are distinguished primarily by their respective ability to infect vertebrates (including humans) versus invertebrates. Being genetically limited, most parvoviruses require actively dividing host cells and are host and/or tissue specific. Some cause diseases, which range from subclinical to lethal. A few require co-infection with helper viruses from other families. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the Parvoviridae, which is available at www.ictv.global/report/parvoviridae. Table 1. Characteristics of the family Parvoviridae Typical member: human parvovirus B19-J35 G1 (AY386330), species Primate erythroparvovirus 1, genus Erythroparvovirus, subfamily Parvovirinae Virion Small, non-enveloped, T=1 icosahedra, 23–28 nm in diameter Genome Linear, single-stranded DNA of 4–6 kb with short terminal hairpins Replication Rolling hairpin replication, a linear adaptation of rolling circle replication. Dynamic hairpin telomeres prime complementary strand and duplex strand-displacement synthesis; high mutation and recombination rates Translation Capped mRNAs; co-linear ORFs accessed by alternative splicing, non-consensus initiation or leaky scanning Host range Parvovirinae: mammals, birds, reptiles. Densovirinae: insects, crustacea, echinoderms Taxonomy Two subfamilies, Parvovirinae and Densovirinae; 13 genera, >75 species VIRION GENOME Viruses package a single copy of a linear ssDNA molecule of Parvovirus virions are small, rugged, non-enveloped 4–6 kb, which contains a long coding region bracketed by protein particles with T=1 icosahedral symmetry short (120–600 nt) dynamic hairpin termini that mediate (Table 1 and Fig. 1). A single coat protein sequence is DNA replication (Fig. 2). Packaged strands can be of negative expressed as a nested set of virion proteins (VP) with or both senses. Two gene cassettes encode a a common C-terminal domain that forms the virion replication initiator protein (NS1 or Rep) and a virion protein shell. VP1 N-termini may have phospholipase A2 (VP), plus a few small genus-specific auxiliary proteins. Many (PLA2) activity [1, 2]. parvoviruses are highly specialized for infecting particular host Received 11 September 2018; Accepted 13 December 2018; Published 23 January 2019 Author affiliations: 1Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520- 8035, USA; 2Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA; 3Department of Biology, Memorial University of Newfoundland, St John’s, NL A1B3X9, Canada; 4National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA; 5Institute of Virology, University of Bonn Medical Centre, Bonn D-53105, Germany; 6MRC - University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK; 7INRA-Universite de Montpellier, 34095 Montpellier Cedex 5, France; 8Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA; 9Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA; 10Department of Virology, University of Helsinki, FIN-00014 University of Helsinki, Finland; 11Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8035, USA; 12Centre de Recherche de Microbiologie et Biotechnologie, INRS-Institut Armand-Frappier Laval, QC H7V 1B7, Canada. *Correspondence: Susan F. Cotmore, [email protected] Keywords: Parvoviridae; Parvovirinae; Densovirinae; taxonomy; ICTV Report. Abbreviations: NS1/Rep, replication initiator protein; PLA2, phospholipase A2; VP, virion protein. 001212 Downloaded from www.microbiologyresearch.org by This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. IP: 128.214.144.149 367 On: Tue, 26 Mar 2019 10:35:49 Cotmore et al., Journal of General Virology 2019;100:367–368 genomic 3¢-hairpin primes complementary strand synthesis by a host replication fork. This creates a duplex transcription tem- plate,allowing RNApolymerase II transcription toinitiate gene expression(Fig.2) DNA replication proceeds via a ‘rolling hairpin’ mechanism, whichreliesonsequentialunfoldingandrefoldingofthehairpin termini.Unidirectionalstranddisplacementsynthesisgenerates continuous duplex intermediates, from which progeny single strandsareexcisedbytheendonucleaseactivityofNS1.Progeny genomes are packaged into preassembled viral particles by the NS1 helicase, via a portal at one of the icosahedral 5-fold axes. Progeny virions may be rapidly exported from living cells, or accumulate in the nucleus until liberated by cell lysis. Many Fig. 1. Virion morphology. Three-dimensional X-ray diffraction struc- virusescausemilddisease,whereasothers,suchascanineparvo- tures of exemplar parvoviruses at 3.1–3.4 Å resolution, obtained using virus (species Carnivore protoparvovirus 1) and most members PDBs 1MVM and 3P0S. Colour depicts distance from the virus centre; ofthesubfamilyDensovirinae,arehighlypathogenic[2,5]. triangles outline one of 60 icosahedral units showing the 2-, 3- and 5- fold axes of symmetry. TAXONOMY Members of the subfamily Parvovirinae infect vertebrates (mammals, birds and reptiles). This subfamily includes eight genera; Bocaparvovirus, Dependoparvovirus, Erythroparvovi- rus, Protoparvovirus, Tetraparvovirus, Amdoparvovirus, Ave- parvovirus and Copiparvovirus, containing >55 species. Viruses thatinfecthumansarepresentinsevenspeciesfromthefirstfive genera in this list. Members of subfamily Densovirinae infect invertebrates (insects, crustaceans and echinoderms). This sub- family contains one unassigned species and five genera; Ambi- densovirus, Brevidensovirus, Hepandensovirus, Iteradensovirus andPenstyldensovirus,comprising>20 species. RESOURCES FullICTVReportonthefamilyParvoviridae: www.ictv.global/report/parvoviridae. Fig. 2. Parvovirus genome organization shows genus- Funding information specific variations. Terminal hairpins are magnified relative to the cod- Production of this summary, the online chapter and associated resources was funded by a grant from the Wellcome Trust ing region to show predicted secondary structures. ORFs are indicated (WT108418AIA). by arrowed boxes. Angled arrows indicate transcriptional promoters and AAAAA indicates polyadenylation sites. Acknowledgements Members of the ICTV 10th Report Consortium are Elliot J. Lefkowitz, Andrew J. Davison, Stuart G. Siddell, Peter Simmonds, Sead Sabanad- cells. Since host restrictions may be relaxed when cells undergo zovic, Donald B. Smith, Richard J. Orton and Balazs Harrach. oncogenic transformation, viruses in some species, such as Conflicts of interest Rodent protoparvovirus 1, may be preferentially oncolytic [3]. The authors declare that there are no conflicts of interest. 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AAV-mediated gene therapy for research metastable [1]; in endosomes some undergo a conformational and therapeutic purposes. Annu Rev Virol 2014;1:427–451. shift, exposing VP1 PLA2 domains required for lipid bilayer 5. Kailasan S, Agbandje-Mckenna M, Parrish CR. Parvovirus family penetration. Intact virions enter the nucleus, where their conundrum: what makes a killer? Annu Rev Virol 2015;2:425–450. Downloaded from www.microbiologyresearch.org by IP: 128.214.144.149368 On: Tue, 26 Mar 2019 10:35:49.